Fluorescent chemical sensors for small organic compounds will be developed. Chemical sensors are synthetic probes which produce a visible signal upon interaction with a specific analyte. In the biochemical community, these probes have been used as sensitive, nondestructive methods for quantifying the concentration of a particular analyte in cells. Chemical sensors have played a pivotal role in unraveling the cellular function of a number of metal ions, most notably cell calcium. Similar fluorescent sensors for organic molecules have not reached this level of success.
The specific aims of this research are to develop novel chemical sensors for neurotransmitters and neuromodulators. This is an important problem with broad ramifications. This project will produce sensors for glutamate, aspartate, lysine, and the catecholamines which function under physiologically relevant conditions of pH and salinity. Furthermore, fluorophores which are pH dependant will be produced to expand the utility of this class of sensors. Biological studies will be performed with the aid of collaborators in which cells will be stained with the fluorescent sensors and the location and concentration of neurotransmitter will be measured.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059245-10
Application #
7449746
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
1999-05-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
10
Fiscal Year
2008
Total Cost
$241,362
Indirect Cost
Name
University of Missouri-Columbia
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Avetta, Christopher T; Shorthill, Berkeley J; Ren, Chun et al. (2012) Molecular tubes for lipid sensing: tube conformations control analyte selectivity and fluorescent response. J Org Chem 77:851-7
Zhang, Shaohui; Glass, Timothy E (2010) An indicator displacement assay with independent dual wavelength emission. Tetrahedron Lett 51:112-114
Dalgarno, Scott J; Claudio-Bosque, Karla M; Warren, John E et al. (2008) Interpenetrated nano-capsule networks based on the alkali metal assisted assembly of p-carboxylatocalix[4]arene-O-methyl ether. Chem Commun (Camb) :1410-2
Plante, Jeffrey P; Glass, Timothy E (2006) Shape-selective fluorescent sensing ensemble using a tweezer-type metalloreceptor. Org Lett 8:2163-6
Shorthill, Berkeley J; Avetta, Christopher T; Glass, Timothy E (2004) Shape-selective sensing of lipids in aqueous solution by a designed fluorescent molecular tube. J Am Chem Soc 126:12732-3
Secor, Kristen E; Glass, Timothy E (2004) Selective amine recognition: development of a chemosensor for dopamine and norepinephrine. Org Lett 6:3727-30
Feuster, Ellen K; Glass, Timothy E (2003) Detection of amines and unprotected amino acids in aqueous conditions by formation of highly fluorescent iminium ions. J Am Chem Soc 125:16174-5
Shorthill, Berkeley J; Granucci, Robert G; Powell, Douglas R et al. (2002) Synthesis of 3,5- and 3,6-linked calix[n]naphthalenes. J Org Chem 67:904-9
Raker, Joseph; Glass, Timothy E (2002) Selectivity via cooperative interactions: detection of dicarboxylates in water by a pinwheel chemosensor. J Org Chem 67:6113-6
Raker, J; Glass, T E (2001) Cooperative ratiometric chemosensors: pinwheel receptors with an integrated fluorescence system. J Org Chem 66:6505-12